Effects Of Arsenic Trioxide On The Gene Expression Of Toll-Like Receptor9, Interferon Regulator Factors5 And Interferon-α Realese In Sle Patients

Objective:To investigate the expression of toll like receptor-9 (TLR9) mRNA, interferon regulatory factors-5 mRNA(IRF5) and interferon-α(IFN-α) of AS₂O₃ on peripheral blood mono-nuclear cells (PBMCs) in Systemic lupus erythematosus (SLE) patients,which may provide theoretical basis for the clinical therapy of Systemic lupus erythematosus.Methods:Isolating and collecting PBMCs and sera from 15 SLE patients and 15 healthy subjects, PBMCs were treated with cyclophosph -amide(CTX)and different concerntration of AS₂O₃ in vitro;real-time quantitative polymerase chain reaction was used to amplify TLR9 and IRF5 gene before drug intervention and after 12 and 24 hours and the mRNA expression was measured; IFN-αin sera and in supernatant liquid after drug intervention were measured with enzyme-linked immunosorb- ent assay( ELISA).Result: 1.The expression of TLR9mRNA, IRF5mRNA on PBMCs and IFN-αin sera in Systemic lupus erythematosus (SLE) patients were obviously higher than that of healthy control group(p<0.05); the IFN-αin sera was not only highly correlated with the expression of TLR9mRNA on PBMCs (Pearman r=0.896 ,P<0.01)but also highly correlated with the mRNA expression of IRF5 on PBMCs (Spearman r=0.658, P<0.01), moreover, the expression of TLR9mRNA was highly correlated with the expression of IRF5 mRNA (Pearman r=0.782, P<0.01).2. AS₂O₃ can suppress the expression of TLR9mRNA on PBMCs and the effect was gradually increasing in the wake of the increasing concerntrations of AS₂O₃ and processing time. AS₂O₃ can also suppress the secretion of IFN-αby PBMC but AS₂O₃ showed a more significant effect in respect of suppressing the expression of TLR9mRNA and IFN-αon SLE group than that of control group, and statistically analysis had significant difference(p<0.05).CTX can also inhibit the expression of TLR9mRNA and IFN-αbut evoke no significant difference in SLE group and control group (P>0.05).Comparing with CTX , AS₂O₃ had more significant effect on inhibiting the expression of TLR9mRNA and IFN-αin SLE patients (p<0.05).3.The expression of IRF5mRNA on PBMCs was not suppressed by AS₂O₃ and CTX,and there was no statistics difference between different groups(P>0.05).Conclusion: we demonstrasted that AS₂O₃ may suppress the TLR9mRNA expression and lead to down regulation of the secretion of IFN-αin SLE patients,which may be one mechanism of clinical treatm- ent.